Neonatal iron distribution and infection susceptibility in full term, preterm and low birthweight babies in urban Gambia: study protocol for an observational study.

James H Cross,Ousman Jarjou,Nuredin Ibrahim Mohammed,Andrew M Prentice,Carla Cerami

doi:10.12688/gatesopenres.12963.2

Abstract

Background: Neonatal infection is the third largest cause of death in children under five worldwide. Nutritional immunity is the process by which the host innate immune system limits nutrient availability to invading organisms. Iron is an essential micronutrient for both microbial pathogens and their mammalian hosts. Changes in iron availability and distribution have significant effects on pathogen virulence and on the immune response to infection. Our previously published data shows that, during the first 24 hours of life, full-term neonates have reduced overall serum iron. Transferrin saturation decreases rapidly from 45% in cord blood to ~20% by six hours post-delivery. Methods: To study neonatal nutritional immunity and its role in neonatal susceptibility to infection, we will conduct an observational study on 300 full-term normal birth weight (FTB+NBW), 50 preterm normal birth weight (PTB+NBW), 50 preterm low birth weight (PTB+LBW) and 50 full-term low birth weight (FTB+LBW), vaginally-delivered neonates born at Kanifing General Hospital, The Gambia. We will characterize and quantify iron-related nutritional immunity during the early neonatal period and use ex vivo sentinel bacterial growth assays to assess how differences in serum iron affect bacterial growth. Blood samples will be collected from the umbilical cord (arterial and venous) and at serial time points from the neonates over the first week of life. Discussion: Currently, little is known about nutritional immunity in neonates. In this study, we will increase understanding of how nutritional immunity may protect neonates from infection during the first critical days of life by limiting the pathogenicity and virulence of neonatal sepsis causing organisms by reducing the availability of iron. Additionally, we will investigate the hypothesis that this protective mechanism may not be activated in preterm and low birth weight neonates, potentially putting these babies at an enhanced risk of neonatal infection. Trial registration: clinicaltrials.gov ( NCT03353051) 27/11/2017.

Highlights

Neonatal infections – challenges in low-income settings Neonatal infection is the third largest cause of death in children under-five worldwide and is an ongoing major global public health challenge (Sustainable Development Goal 3.2)1
An increasing proportion of child deaths are in sub-Saharan Africa5, with 60–80% of newborn deaths occurring in low birthweight (LBW) neonates (
We hypothesize that premature and/or low birthweight babies have a defect in their ability to sequester iron at 6–24 hours after birth in comparison to full term neonates with normal birthweight

Summary

Introduction

Neonatal infections – challenges in low-income settings Neonatal infection is the third largest cause of death in children under-five worldwide and is an ongoing major global public health challenge (Sustainable Development Goal 3.2). An increasing proportion of child deaths are in sub-Saharan Africa, with 60–80% of newborn deaths occurring in low birthweight (LBW) neonates (

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